{"title":"The different paradigms of NK cell death in patients with severe trauma.","authors":"Te-Ding Chang, Deng Chen, Jia-Liu Luo, Yu-Man Wang, Cong Zhang, Shun-Yao Chen, Zhi-Qiang Lin, Pei-Dong Zhang, Ting-Xuan Tang, Hui Li, Li-Ming Dong, Ning Wu, Zhao-Hui Tang","doi":"10.1038/s41419-024-06992-0","DOIUrl":null,"url":null,"abstract":"<p><p>Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.</p>","PeriodicalId":9734,"journal":{"name":"Cell Death & Disease","volume":null,"pages":null},"PeriodicalIF":8.1000,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339281/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell Death & Disease","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1038/s41419-024-06992-0","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Lymphocyte decline, particularly the depletion of NK cells, is a prominent feature of immunosuppression following severe tissue injury, heightening the susceptibility of severe trauma patients to life-threatening infections. Previous research indicates that the reduction in the number of NK cells is closely associated with the process of cell death. Nonetheless, the precise mechanism of NK cell death remains unknown. Here, we discovered that following severe traumatic injury, NK cells undergo several cell death pathways, dominated by apoptosis and pyroptosis with coexistence of necrotic cell death, immunogenic cell death, ferroptosis, and autophagy. These NK cells with different paradigms of death have diverse cytokine expression profiles and diverse interactions with other immune cells. Further exploration revealed that hypoxia was strongly associated with this diverse paradigm of NK cell death. Detailed investigation of paradigms of cell death may help to enhance comprehension of lymphopenia post-severe trauma, to develop new strategy in preventing immunosuppression, and then to improve outcome for severe trauma population.
淋巴细胞的减少,尤其是 NK 细胞的耗竭,是严重组织损伤后免疫抑制的一个突出特征,使严重创伤患者更容易受到危及生命的感染。以往的研究表明,NK 细胞数量的减少与细胞死亡过程密切相关。然而,NK细胞死亡的确切机制仍然未知。在这里,我们发现严重创伤后,NK 细胞会经历多种细胞死亡途径,其中以细胞凋亡和热凋亡为主,坏死细胞死亡、免疫原性细胞死亡、铁凋亡和自噬并存。这些具有不同死亡模式的 NK 细胞具有不同的细胞因子表达谱以及与其他免疫细胞的不同相互作用。进一步的研究发现,缺氧与 NK 细胞的不同死亡模式密切相关。对细胞死亡模式的详细研究可能有助于加深对严重创伤后淋巴细胞减少症的理解,制定预防免疫抑制的新策略,进而改善严重创伤人群的预后。
期刊介绍:
Brought to readers by the editorial team of Cell Death & Differentiation, Cell Death & Disease is an online peer-reviewed journal specializing in translational cell death research. It covers a wide range of topics in experimental and internal medicine, including cancer, immunity, neuroscience, and now cancer metabolism.
Cell Death & Disease seeks to encompass the breadth of translational implications of cell death, and topics of particular concentration will include, but are not limited to, the following:
Experimental medicine
Cancer
Immunity
Internal medicine
Neuroscience
Cancer metabolism